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This phase I trial studies the side effects and best dose of recombinant interleukin-15 in treating patients with melanoma, kidney cancer, non-small cell lung cancer, or head and neck cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment. Recombinant interleukin-(IL)15 is a biological product, a protein, made naturally in the body and when made in the laboratory may help stimulate the immune system in different ways and stop tumor cells from growing.

I. To determine the effect of the dose schedules of rhIL15 on the number and phenotype of peripheral blood mononuclear cells including: total white blood cell count; absolute lymphocyte count (ALC); and total number of T cells and natural killer (NK) cells, as well as activated T cells, T cell subsets and NK cell subsets.

Patients receive recombinant interleukin-15 subcutaneously (SC) daily on days 1-5 of weeks 1 and 2. Treatment repeats every 28 days (4 weeks) for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 24 weeks.

Patients receive recombinant interleukin-15 SC daily on days 1-5 of weeks 1 and 2. Treatment repeats every 28 days (4 weeks) for up to 6 courses in the absence of disease progression or unacceptable toxicity.

MTD defined as the next lower dose in which 1 or more patients experiences a dose limiting toxicity defined as grade 3 or 4 toxicity graded according to the NCI Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: 28 days ]

Secondary Outcome Measures
:

ALC, monitored daily during treatment [ Time Frame: Up to 6 months ]

The absolute increase in each cell subset as well as the variance in change across each dose level (mean, median, and SE/SD will be reported for each dose level and ALC, circulating NK count, and circulating CD4/CD8 cell counts).

The absolute change in responses for each patient will be calculated by subtracting the SFC/million PBMC at day 11 from the SFC/million PBMC at baseline for each antigen.

Change in presence of auto-antibodies, assessed by ELISA [ Time Frame: Baseline to day 4 of week 2 ]

The number and percentage of patients developing auto-antibodies to IL15 will be tabulated by dose cohort.

Change in T cell responses to non- physiologic stimuli including PMA [ Time Frame: Baseline to day 4 of week 2 ]

The absolute change in responses for each patient will be calculated by subtracting the SFC/million PBMC at day 11 from the SFC/million PBMC at baseline for each antigen.

Change in T cell subset response to recall viral antigens including CMV and influenza A virus, determined by enzyme-linked immunosorbent spot assay [ Time Frame: Baseline to day 4 of week 2 ]

The absolute change in responses for each patient will be calculated by subtracting the spot forming cells (SFC)/million peripheral blood mononuclear cell (PBMC) at day 11 from the SFC/million PBMC at baseline for each antigen.

Change in total number of T cells and NK cells, as well as activated T cells, T cell subsets, and NK cell subsets, assessed by flow cytometric analysis of peripheral blood mononuclear cells [ Time Frame: Baseline to day 15 ]

The percentage of cells positive for the marker and/or mean fluorescence intensity (MFI) at time points after rhIL15 administration will be compared to baseline and the change will be calculated as %after/ %baseline or MFI after/ MFI baseline.

ORR based on RECIST criteria [ Time Frame: Up to day 56 (after 2 courses) ]

Percentages and exact 2-sided 95% confidence intervals of the numbers in each of the overall response categories (complete response, partial response, stable disease and progressive disease) will be calculated for each dose cohort.

The absolute increase in each cell subset as well as the variance in change across each dose level (mean, median, and standard error [SE]/standard deviation [SD] will be reported for each dose level and absolute lymphocyte count [ALC], circulating NK count, and circulating CD4/CD8 cell counts).

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Ages Eligible for Study:

19 Years and older (Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patients must have histological or cytological confirmed malignancy in the following disease groups: melanoma, non-small cell lung carcinoma, renal cell carcinoma or squamous cell head and neck carcinoma, for which no standard effective or curative options are available

No known central nervous system (CNS) metastases or neurological symptoms possibly related to active CNS metastasis

Females of childbearing potential must have a negative pregnancy test within 48 hours prior to initiation of protocol therapy; NOTE: subjects are considered not of child bearing potential if they are surgically sterile, they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy or they are postmenopausal; menopause is the age associated with complete cessation of menstrual cycles, menses, and implies the loss of reproductive potential; by a practical definition, it assumes menopause after 1 year without menses with an appropriate clinical profile at the appropriate age; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time the consent is signed and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; women of child-bearing potential and men treated or enrolled on this protocol must also agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) 4 months after completion of rhIL15

Ability to understand and the willingness to sign a written informed consent document

No systemic or inhaled corticosteroids within 7 days prior to initiation of protocol therapy; NOTE: use of topical corticosteroids and/or eye drops containing glucocorticosteroids is acceptable

No immunosuppressive therapy within 30 days prior to initiation of protocol therapy

No history of severe asthma, as defined by prior or current use of systemic corticosteroids for disease control, with the exception of physiological replacement doses of cortisone acetate or equivalent, as defined by a dose of 10 mg or less; NOTE: history of mild asthma not requiring daily therapy is eligible

No history of pulmonary disease such as emphysema or chronic obstructive pulmonary disease (COPD), (forced expiratory volume in one second [FEV1] > 2L or >= 50% of predicted for height and age); pulmonary function tests (PFTs) are required in patients with significant pulmonary or smoking history

Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal, barrier method of birth control or abstinence) from the time the consent is signed, during the duration of study participation and 4 months after discontinuation of protocol therapy

No platelet or blood transfusions within two weeks of obtaining baseline laboratory values

No blood modifiers while enrolled in the study (i.e., growth factors such as erythropoiesis-stimulating agent [ESA] or filgrastim [G-CSF]); NOTE: blood transfusions are allowed per institutional guidelines

Exclusion Criteria:

Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C), or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

Class II or greater congestive heart failure as described in the New York Heart Association Functional Classification criteria

Patients with thyroid disease should be excluded unless their T4 is normal or they are on replacement therapy

Patients with primary brain cancer or known brain metastases should be excluded from this clinical trial

Patients who have received prior anti-CTLA4 or anti-PD1 therapy less than 8 weeks prior to enrollment

Patients who have received prior biologic agents less than 4 weeks prior to enrollment

Patients who have received prior interferon or IL-2 therapy less than 4 weeks prior to enrollment